Professor Severin has lucked out twice. He was the first in the world to develop a cancer vaccine and then he found an investor who trusted him. Over five million dollars have been invested in this project, now in its second stage of clinical trials

Galina Kostina

Professor Sergei Severin, Corresponding Member of the Russian Medical Academy, had long been involved in comprehensive cancer treatment. He worked within the global biotechnology mainstream developing targeted delivery of drugs to malignant cells. Severin even created a structure of his own, one based on a protein, the epidermal growth factor. At the same time, he was thinking about metastases formation. He attempted to fight them using special proteins able to block vascular invasion. He ran experiments on mice inoculating them against skin cancer, melanoma. The investigations proceeded more or less successfully but both Severin and global oncology were a long way from a revolution in cancer treatment. While Severin was treating mice, Alexei Kotelevets, a plastic surgeon, was writing his Ph.D. dissertation between operations on well-to-do beauties. It addressed the special gel preparations used in cosmetology and plastic surgery to mold faces and smooth out wrinkles by making gel “pads” of constant volume in desired areas. The gel stays in the pads for a couple years and then dissolves. Along with the fashion for gel injections, the question of whether they were harmless arose and Kotelevets decided to conduct trials on Severin’s mice to prove the gel’s safety. The results of these simple experiments brought about a sensational turn in Severin’s research as well as in global cancer studies.

The melanoma vaccine

During the course of the experiment, the scientists discovered that a blob of gel injected under a mouse’s skin several months previously was circled by connective tissue cells and that blood vessels had managed to permeate this capsule-like structure. The plastic surgeon would most likely have ignored this, but it excited Severin. In theory, foreign cells could be placed in the capsule and could “train” the body’s immune system. Thanks to the capsule, they would be protected against immune forces, which, as a rule, seek to kill alien cells, and thanks to the blood vessels, they could survive inside the capsule while transmitting information about themselves to the immune system. As a result, new immunity is stimulated, and in essence, this is a new type of vaccination technology. The very first experiments on rats when the gel was administered first and then a month later cells from a mouse were injected into the gel capsule proved this assumption. Thus, by pure accident, Sergei Sevein and his colleagues found a solution what other scientists worldwide had been attempting unsuccessfully: how to keep maintain the cells of one mammal in the body of another (for example, mouse melanoma cells in the human body) for the purpose of vaccination against a number of cancers. Researchers in various countries had tried just about everything. Some even tried porous metal as a protective capsule. However, luck was not with them. Severin’s group continued to test the new vaccination technique on mice. They injected human melanoma cells in the gel capsule. “After a time, we observed that the capsule was covered with a thick layer of lymphocytes: having scented strangers through the protective shell, they attacked the capsule but were unable to break through and had completely surrounded it,” Severin relates. “After that, in one of the trials, we took the lymphocytes off the capsule and put them in a Petri dish with mouse melanoma, which they killed. Note that the lymphocytes, which had only communicated with the human melanoma cells through the capsule wall, remembered it and transferred their anger to the similar mouse melanoma, although they had never seen it before in their lives.”
Thus, the experiments proved that capsule-protected foreign melanoma cells could train and stimulate specific immunity targeting a specific disease in the body. Why do immune cells need this training? The problem is that the human immune system attacks a tumor rather listlessly. It apparently sees malignant cells as both foreign and at the same time as normal parts of the body. Trained for foreign melanoma, human immune cells after vaccination will not allow a tumor to form. The same method can be used to prevent metastases formation. However, this can be done only after the main tumor has been killed. In the presence of a tumor, it is pointless and even harmful to inject foreign mouse cells, as they would attract the body’s already weak immune forces. As the new development was truly pioneering, Severin was anxious about intellectual property rights and obtained the Russian patent both for the encapsulating technique and for cultivating cells inside the capsule.

Cleopatra convinces investors

The fact that clinical trials are under way is already a success: often, developers don’t even get that far. Trials are often beyond the means of Russia’s publicly funded scientific institutions that live mostly off foreign grants.
Severin also sought a foreign investor. He did what he could by participating in international symposia or making attempts to persuade wealthy friends in Russia to contribute. However, foreigners tried to get as much information as possible without mentioning money, while rich Russians didn’t want to part with their money for a long period of time. Then Severin had another stroke of luck. His original collaborator, Alexei Kotelevets, told his old acquaintance, lawyer Yulia Mozharenko, about the unexpected results of the gel experiments. Mozharenko decided to familiarize herself with the development in more detail. Stunned by the scientists’ achievements, she introduced them to her acquaintance and business partner Sergei Generalov, head of Industrial Investors Group (Promyshlennye Investory).
“Cleopatra the dog made a profound impression on us,” Mozharenko recalls. “She was dying of the final stages of breast cancer. After the new technology was applied, Cleopatra apparently felt better. In six months, examination revealed the complete disappearance of metastases and the substantial reduction in size of the tumor itself.” Generalov decided to allocate some funds to the scientists as charity donation, saying that combating cancer was a noble cause. However, he took a keen interest in the results of the trials.
Generalov had not tried his hand at venture projects before he met Severin. Of course, direct investment in tractors or vodka can also be risky, but it’s still a well-calculated business. The meeting with the scientists prompted Generalov to look closely at biotechnology, a very unusual industry for him. “Properly speaking, the rapid development of global biotechnology in breakthrough areas, where more than $14 billion were invested last year, and the unique development of our scientists induced me to move from charity to deliberate investment,” says Generalov.
Thus, in 2002 Russian Biotechnologies (Russkiye Biotekhnologii) was founded with Sergei Severin’s group (49%) and Industrial Investors (51%) as shareholders. Recognition is wonderful, but it can’t replace commercialization. “The investors set a specific task before the new company – to create and enhance assets, including intangible ones,” says Alexander Krivonos, General Director of Russian Biotechnologies. Patenting the procedure abroad was the first thing managers addressed with Mozharenko’s assistance. The application for the European patent valid for a large number of countries has already been filed, as well as patents for the US, Canada, China, Korea, Japan, and New Zealand.
Creating tangible assets means building modern laboratory and production facilities that meet ISO and GMP standards and that are certified by international organizations. In these facilities, scientists will work on a number of other promising developments, including a project on production of cellular medications (fibroblasts) designed to treat and restore damaged skin and an antibody-based express diagnostic system for various cancers, viruses, and bacteria. Finally, the lab is working on a popular project to cultivate, preserve, and differentiate stem cells and on providing services to cosmetology and health care institutions. Severin’s group has already developed the necessary techniques, but the company has put a hold on this area until legislative acts regulating this field have been passed. Each project has the potential to become a real source of income with time. After reviewing these plans, Industrial Investors decided in early June to invest $5.2 million in Russian Biotechnologies over the next four years.
 
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